1. Field of the Invention
The invention relates to an oral pharmaceutical preparation containing omeprazol, the chemical name of which is 5-methoxy-2-(((3,5-dimethyl-4-methoxy-2-pyridinyl)methyl)sulfinyl)-1H-benz imidazole, of formula: ##STR1## or an alkali salt thereof.
2. Reference to the Prior Art
The synthesis of these compounds is disclosed by the present inventor in Spanish patents nos 9002764, 9003113 and 9003174.
Omeprazol is a very effective drug for the treatment of gastric and duodenal ulcers.
Omeprazol is stable at basic pH, but rapidly decomposes at neutral or acid pH. Likewise, moisture has a negative effect on the stability of the compound. Therefore, if omeprazol is administered orally, it must be protected from the gastric juices, which are acid, so that it may reach the small intestine where it is absorbed, in unaltered state (GB-2,189,698-A).
This protection is achieved by covering the omeprazol nucleus with an enteric coating, insoluble in an acid medium but soluble or readily disintegratable in a neutral or basic medium. Nevertheless, the compounds regularly used for this purpose are acid, whereby the nucleus tends to discompose with time. (GB-2,189,698-A)
This problem is solved in part by increasing the basic response of the nucleus, either by introducing the omeprazol in alkali or alkali earth salt form, or by mixing the omeprazol with a basic compound, or by combining both possibilities. In this way a basic micro-pH is formed around the omeprazol particles, increasing the stability thereof, but it does not eliminate the contact of the omeprazol with the acid enteric coating.
The fact that the nucleus is basic causes a further problem. The outer layer is water permeable in part, so that after administration of the drug the water in the digestive channel could reach the nucleus and dissolve it in part. The alkaline solution thus formed would thereafter attack the enteric coating, finally causing premature destruction thereof.
These difficulties are overcome by interposing a first coating formed by one or more separation layers of an appropriate nature between the nucleus and the enteric coating. For the preparation of these layers there is used a compound or polymer used for film coating which is inert, water soluble and pharmacologically acceptable, for example sugar, polyethylene glycol or polyvinyl alcohol, possibly accompanied by a basic compound. This first or internal coating separates the omeprazol from the external acid coating. It furthermore has the secondary function of acting as a pH buffer zone, such that the stomach acidity may not penetrate to the nucleus and the basicity of the nucleus may not affect the enteric coating (GB-2, 189,698-A).
Of course, the basic compounds cited in the foregoing paragraphs must be physiologically acceptable. To be precise, for omeprazol, the literature cites the Na, K, Ca, Mg and Al salts of weak organic or inorganic acids, such as citric, phosphoric or carbonic acid and the oxides and hydroxides of Ca, Mg and Al (GB-2.189.698-A).